The compound endo-1-methyl-N-(9-methyl-9-azabicycle[3.3.1]non-3-yl)-1H-indazole-3-carboxamide, which has been assigned the INN granisetron:
is disclosed in patent EP 200444. It acts as antagonist of 5-HT (5-hydroxytriptamine) and is useful as an anti-emetic. Said patent discloses how it is made by reaction of 1-methylindazole-3-carboxylic acid chloride with endo-3-amino-9-methyl-9-azabicycle-[3.3.1]-nonane.
Other processes for preparing granisetron were later disclosed. In patent ES 2129349 it is obtained by reaction of 1-methylindazole-3-carboxylic acid with a compound of structure (1):
in which X represents an isocyanate group or a group that can generate an isocyanate group when heated.
International application WO 9730049 discloses an alternative process for preparing granisetron, by cyclisation of a previously methylated compound of formula (2):

It should be noted that the methylation prior to cyclisation is carried out with sodium hydride and methyl iodide as disclosed in example 1 (b) of said international application. However, the cyclisation conditions applied to that compound of formula (2) may facilitate demethylation of the indazole N of the granisetron so obtained.
Thus, for example, examples 2 and 3 of said international application describe the cyclisation reaction, but although in Example 2 the reaction leads to granisetron, in Example 3, when the reaction time is increased under the same conditions, quantitatively demethylated granisetron is provided.
The reaction time therefore has a considerable influence on the yield values in the second step of the process, that is, in the cyclisation step, since the granisetron provided by this process contains as an impurity significant amounts of demethylated granisetron which will have to be remethylated in an additional step.
Moreover, it should not be forgotten that the methylating agent used in the methylation is methyl iodide, a carcinogenic and highly volatile compound (b.p.=41°–43° C.).
Therefore, although said international application discloses a process for preparing granisetron by methylation followed by cyclisation, it should be stressed that the yield from the last step may be very low, in which case a third step would have to be carried out, that is, a further methylation which presents the disadvantages mentioned in the preceding paragraph, in order to yield the granisetron free from demethylated granisetron.